Recent analyzes show that pregnant women and newborns may face an increased risk of developing more severe cases of COVID-19 after SARS-CoV-2 infection.
A new study led by investigators from Massachusetts General Hospital (MGH) and published in Cell reveals the transfer of protective antibodies to SARS-CoV-2 lower than expected across the placenta from mothers infected in the third trimester. The cause may be changes in these antibodies after they are produced – a process called glycosylation.
The results extend to recent team findings published in JAMA network open that pregnant women with COVID-19 do not transmit the SARS-CoV-2 virus, but also relatively low levels of antibodies against it, in newborns.
For this latest study, scientists compared maternal antibodies against influenza (flu), whooping cough (pertussis) and SARS-CoV-2 and the way these antibodies were transmitted through the placenta.
Antibodies specific for influenza and pertussis were actively transmitted in a relatively normal manner. In contrast, the transfer of SARS-CoV-2-specific antibodies to the baby was not only significantly reduced, but the transferred antibodies were less functional than anti-influenza antibodies. Decreased transmission was observed only in third trimester infection.
The researchers found that altered carbohydrate bonds with specific antibodies to SARS-CoV-2 – a process called glycosylation – may be to blame for this reduced transmission from mother to fetus in the third trimester. Carbohydrate attachments to antibodies specific for SARS-CoV-2 in maternal blood were different from those seen on antibodies specific for influenza and pertussis.
This pattern of carbohydrates can cause COVID-specific antibodies to “get stuck” in the maternal circulation, instead of being transmitted across the placenta via placental antibody receptors.
The increase in total maternal antibodies caused by infection, as well as the greater expression of placental expression of antibody receptors that attract a carbohydrate sample to antibodies specific for SARS-CoV-2, helped to partially overcome the problem and facilitate the transfer of some functional antibodies from mother to fetus.
Interestingly, some of the antibodies that were best transmitted were also the most functional, activating natural killer cells that could help the newborn fight the virus if exposed.
The findings have implications for the design of SARS-CoV-2 vaccines for pregnant women.
Vaccine regimens capable of driving high levels of COVID-specific antibodies with glycosylation patterns favored by the placenta for selective transmission to the fetus may lead to better protection of newborns and infants. “
Andrea Edlow, Ph.D. Med., MS, co-senior and specialist in maternal and fetal medicine Authora, Massachusetts General Hospital
Edlow is too Assistant Professor of Obstetrics, Gynecology and Reproductive Biology at Harvard Medical School.
Associate and principal member of the Ragon Institute of MGH, MIT, and Harvard, dr. Galit Alter, notes, “For the first time, we are beginning to define rules for the transfer of antibodies to the placenta SARS-CoV-2 – catalyzing our ability to rationally design vaccines to protect pregnant women and their newborns.”
In addition, understanding how antibody transmission varies in the trimester may indicate critical windows in pregnancy that may be most desirable for vaccination to optimize the protection of the mother and her child.
Massachusetts General Hospital
Atyeo, C., and others. (2020) Compromised placental antibody transfer specific for SARS-CoV-2. Cell. doi.org/10.1016/j.cell.2020.12.027.